This invention pertains to novel .alpha.-aryl-.alpha.-(.omega.-aminoalkyl)-.alpha.-[hydroxy(aralkyl and cycloalkyl)]acetic acid derivatives and .alpha.-aryl-.alpha.-(.omega.-aminoalkyl)-.alpha.[alkanoyloxy(aralkyl and cycloalkyl)]acetic acid derivatives, useful in the treatment of cardiovascular disease.
Others have disclosed the synthesis of various .alpha.-aryl-.alpha.-(.omega.-aminoalkyl)-.alpha.-(aralkyl and cycloalkyl)acetic acid derivatives and one .alpha.-aryl-.alpha.-(.omega.-aminoalkyl)-[hydroxy(alkyl)]acetic acid derivative.
The synthesis of various .alpha.-(pyridyl)-.alpha.-(.omega.-aminoalkyl)-.alpha.-[aralkyl, cycloalkyl, alkyl and cycloalkyl(alkyl)]acetic acid derivatives, and measurements of their anti-arrhythmic activities, were reported by C. A. Bernhart et al in "Synthesis and Antiarrhythmic Activity of New [(Dialkylamino)alkyl]pyridylacetamides", J. Med. Chem. 26, 451-455 (1983). In U.S. Pat. No. 4,356,177, the synthesis of .alpha.-(pyridyl)-.alpha.-(.omega.-aminoalkyl)-.alpha.-[cycloalkyl, alkyl, alkenyl, alkynyl, and cycloalkyl (alkyl)]acetic acid derivatives, and, in some instances, measurement of their antiarrhythmic activities were disclosed.
N,N-Dimethyl-4-dimethylamino-2-(1-hydroxypropyl)-2-phenylbutyramide, was described by R. E. Stenseth and Frederich F. Blicke in "Cyclization of Basic Amide Hydrochlorides, A New Synthesis of Substituted Lactams", The Journal of Organic Chemistry 34, 3007-3010 (1969). No biological data was reported.
In addition, various .omega.-amino-2-phenyl-2-pyridylbutyramides and .omega.-amino-2-phenyl-2-pyridylvaleramides, as eurhythmic agents, and the corresponding nitriles were reported in Chemical Abstracts (1963), Column 12522, (which cites Belgium Pat. No. 617,730 and two United States application dates). In U.S. Pat. No. 3,225,054, 4-dipropylamino-2-aryl-2-pyridylalkanamides, as eurhythmic, anti-inflammatory and diuretic agents, and the corresponding nitriles, were described. The synthesis of .alpha.-benzyl-.alpha.-[2-(dimethylamino)ethyl]-2-pyridine acetamide was described in Chemical Abstracts 63, 18019b, but no biological activity was discussed. Phenylacetic acid esters substituted on the .alpha.-carbon with alkyls, alkenes, alkynes, aralkyls, aryls, cycloalkyls, and cycloalkenyls, as well as with (dialkylamino)alkyl and cycloaminoalkyl groups were described in Chemical Abstracts 70, 55926g; some of these had antidepressant activity. British patent specification 771,814, "New Butyryl Amides and Processes for their Manufacture" disclosed disubstituted amides of .alpha.-phenyl-.alpha.-(2-pyridyl)-.omega.-(disubstituted-amino)-butyric acids as antihistaminic and antispasmodic agents.